Electron microscopic visualization of the cross-bridge movement coupled with ATP hydrolysis in muscle thick filaments in aqueous solution, reminiscences and future prospects

Abstract

Although it has been well established that muscle contraction results from cyclic attachment-detachment between the cross-bridges extending from the thick filaments and the sites on the thin filaments, the movement of the cross-bridges coupled with ATP hydrolysis still remains to be a matter for debate and speculation. The most straightforward way to elucidate this mystery is to record individual cross-bridge movement in response to ATP. Using a gas environmental chamber (EC, or hydration chamber), with which biological specimens retaining their physiological function can be observed under an electron microscope, my coworkers and I succeeded in recording the ATP-induced individual cross-bridge movement in two different kinds of synthetic thick filaments in 1997 and 2008. In the synthetic bipolar filaments consisting of rabbit skeletal muscle myosin, the amplitude of cross-bridge movement exhibits a peak at 5-7.5 nm, and the direction of cross-bridge movement is away from, but not towards, the filament bare region in the absence of thin filaments. After exhaustion of ATP, the cross-bridges return towards their initial position, indicating that the initial cross-bridge state may be analogous to that after completion of power stroke. These results constitute the first visualization of the cross-bridge recovery stroke, indicating that the EC is a powerful tool to open new horizons in the research fields of life sciences. © Springer Science+Business Media, LLC 2010.